JP2019524373A - Method and apparatus for neuromodulation of the adrenal gland - Google Patents

Abstract

Aspects of the present disclosure relate to an apparatus, system, and method for performing treatment of a patient's adrenal gland. These devices, systems, and methods can include a lead body that attaches to a portion of a patient's adrenal gland and a plurality of electrodes disposed along the lead body. Also, one or more of the plurality of electrodes can deliver stimulation energy that regulates the release of catecholamines from chromaffin cells in the adrenal gland. [Selection] Figure 6

Description

[Cross-reference with related applications]
This application claims priority to US Provisional Patent Application No. 62 / 378,419, filed August 23, 2016, which is hereby incorporated by reference in its entirety.

  The present disclosure relates to medical devices and methods for providing stimulation therapy. Specifically, the present disclosure relates to an apparatus and method for treating a patient's adrenal gland.

  In various illnesses and disorders, electrical stimulation may be useful for treatment. Leads used in electrical stimulation can be implanted within, near, or near the target site. In some examples, one or more leads can be placed near a nerve, muscle, or other tissue.

  Symptoms including depression, fibromyalgia, chronic fatigue, chronic pain, migraine, orthostatic intolerance, postural orthostatic tachycardia syndrome (POTS) and other medical conditions include adrenal dysfunction, or norepinephrine, Abnormal levels of catecholamines such as epinephrine and dopamine have been associated. Stimulation of the adrenal gland can promote or inhibit the release of catecholamines directly into the bloodstream.

  Visceral nerve prenodal sympathetic axons terminate in adrenal medulla chromaffin cells. Two chromaffin cell populations, one releasing epinephrine and one releasing norepinephrine, exhibit different innervation patterns. As a result, varying these levels independently using different stimulation patterns can drive abnormal levels of catecholamines to normal levels, thereby causing one or more of the various pathologies involved. Therapies and / or treatments for

  Example 1 A device for treating a patient's adrenal gland, wherein the lead body is configured to adhere to a portion of the patient's adrenal gland and engage the adrenal gland, and is disposed along the lead body. A plurality of electrodes, wherein at least one of the plurality of electrodes is configured to deliver stimulation energy that regulates the release of catecholamines from chromaffin cells in the adrenal glands.

  Example 2: The device of Example 1, wherein the lead body is configured to adhere to the adrenal gland or the connective tissue surrounding the gland.

  Example 3: The lead body is configured to adhere to at least one of the connective tissue around the capsule, the outer surface of the adrenal capsule, the inner surface of the adrenal capsule, and the inner and outer surfaces of the adrenal capsule. The apparatus of Example 1 or 2.

  Example 4: A lead body is configured to adhere to a portion of a patient's adrenal gland by at least one of mechanical attachment and adhesive attachment of the lead body to a portion of the patient's adrenal gland or connective tissue around the capsule The apparatus in any one of Example 1-3.

  Example 5 The apparatus of example 4, wherein the lead body further comprises at least one of barbs, suture tabs, a helical structure and a claw for mechanical attachment of the lead body to a portion of the patient's adrenal gland.

  Example 6 The apparatus of example 4, further comprising at least one of tissue glue, adhesive and hydrogel for attachment of the lead body to a portion of the patient's adrenal gland.

  Example 7 The apparatus of any of Examples 1-6, wherein at least one of the plurality of electrodes includes a perforated portion and is configured to enter the adrenal gland.

  Example 8: At least one of a plurality of electrodes configured to invade the adrenal is further configured to deliver stimulation energy that regulates the release of catecholamines from chromaffin cells in the adrenal gland. The apparatus of Example 7.

  Example 9: Patient heart rate, patient heart rate variability, patient respiratory rate, patient activity level, patient catecholamine level, patient catecholamine metabolism, patient normetanephrine level, patient metanephrine level, patient urine At least one of medium creatinine level, patient cortisol metanephrine level, patient posture, patient temperature, patient cardiac output, patient arterial pressure, patient sleep state, and patient sleep depth The apparatus of any of examples 1-8, further comprising a physiological sensor configured to measure

  Example 10 The apparatus of example 9 wherein the stimulation energy is altered in response to at least one of a physiological sensor measurement and a patient input.

  Example 11 The apparatus of example 9, further comprising a controller configured to communicate with the physiological sensor and to command delivery of stimulation energy in response to the communication.

  Example 12: The example further includes a controller configured to command stimulation energy modulating the release of catecholamines from chromaffin cells in the adrenal gland through at least one of the plurality of electrodes. The device according to any one of 1 to 11.

  Example 13 The apparatus of example 12, wherein the controller is configured to command intermittently or continuously to deliver stimulation energy through different electrode sets of the plurality of electrodes.

  Example 14 The apparatus of example 12, wherein the controller is configured to instruct delivery of stimulation energy at a duty cycle based on catecholamine metabolism time through at least one of the plurality of electrodes.

  Example 15 The apparatus of example 12, wherein the controller is configured to instruct delivery of stimulation energy at a frequency between 2 Hz and 20 kHz through at least one of the plurality of electrodes.

  Example 16: Apparatus for treating a patient's adrenal gland, comprising at least one attachment mechanism configured to attach to a portion of the patient's adrenal gland, and configured to engage the adrenal capsule A lead body and a plurality of electrodes disposed along the lead body, the plurality of electrodes through which at least one of the plurality of electrodes allows release of catecholamines from chromaffin cells in the adrenal gland. A device configured to deliver stimulating energy to regulate.

  Example 17 The apparatus of example 16, wherein the plurality of electrodes are disposed on a paddle element disposed at the distal end of the lead body.

  Example 18 The apparatus of Example 17, wherein the paddle element is configured to expand into a deployed configuration in response to deployment from the deployment system and to bend and collapse into a delivery configuration in response to retraction within the deployment system. .

  Example 19: The apparatus of example 17, wherein the paddle element is flexible and is configured to engage and adhere to a portion of the patient's adrenal gland or peri-gland connective tissue in a delivery configuration.

  Example 20 The apparatus of example 16, further or alternatively comprising at least one thermoelectric element configured to cool the adrenal gland to modulate the release of catecholamines from chromaffin cells in the adrenal gland.

  Example 21 The apparatus of example 16, wherein the plurality of electrodes are disposed on a paddle element disposed at a distal end of the lead body and at least one thermoelectric element is disposed with the paddle element.

  Example 22: The lead body is configured to adhere to at least one of peri-gland connective tissue, the outer surface of the adrenal capsule, the inner surface of the adrenal capsule, and the inner and outer surfaces of the adrenal capsule. The apparatus of Example 16.

  Example 23: The apparatus of example 16, wherein the lead body is configured to be attached to a portion of a patient's adrenal gland or peri-gland connective tissue by at least one of mechanical attachment and adhesive attachment.

  Example 24 The apparatus of example 23, wherein the lead body includes at least one of barbs, suture tabs, helical structures and clawes for mechanical attachment.

  Example 25 The apparatus of example 23, further or alternatively comprising at least one of a tissue glue, adhesive and hydrogel for adhesive attachment of the lead body to a portion of the patient's adrenal gland.

  Example 26 The apparatus of example 16, wherein at least one of the plurality of electrodes is configured to penetrate into the adrenal gland and attach the lead body to a portion of the patient's adrenal gland.

  Example 27: A system for treating a patient's adrenal gland, wherein the lead body is configured to engage the adrenal capsule and at least one of the plurality of electrodes disposed along the lead body. A plurality of electrodes configured to deliver stimulatory energy that regulates the release of catecholamines from chromaffin cells in the adrenal gland and a physiology configured to measure at least one physiological response of the patient And a signal operably coupled to the lead and the physiological sensor to command delivery of stimulation energy from at least one of the plurality of electrodes and to have data indicative of at least one physiological response of the patient From the physiological sensor, analyze the signal to calculate the change in stimulation energy, and communicate with the lead based on the analysis of the signal to stimulate the energy System comprising a controller configured to change over.

  Example 28: Physiological sensors include patient heart rate, patient heart rate variability, patient respiratory rate, patient activity level, patient catecholamine level, patient catecholamine metabolism, patient normetanephrine level, patient metanephrine Level, patient urinary creatinine level, patient cortisol metanephrine level, patient posture, patient temperature, patient cardiac output, patient arterial pressure, patient sleep state, and patient sleep depth, 28. The system of embodiment 27 configured to measure at least one of them.

  Example 29 The system of example 27, wherein the controller is further configured to command intermittently or continuously to deliver stimulation energy through different electrode sets of the plurality of electrodes.

  Example 30 The system of example 27, wherein the controller is further configured to instruct delivery of stimulation energy at a duty cycle based on catecholamine metabolism time through at least one of the plurality of electrodes.

  Example 31 The system of example 27, wherein the controller is further configured to instruct delivery of stimulation energy at a frequency between 2 Hz and 20 kHz through at least one of the plurality of electrodes.

  Example 32: A method of treating a patient's adrenal gland, the step of delivering a lead body to the patient's adrenal gland, attaching a portion of the lead body to the patient's adrenal gland or peri-gland connective tissue, Delivering stimulation energy that modulates the release of catecholamines from chromaffin cells in the adrenal gland through at least one of a plurality of electrodes disposed along the body.

  Example 33: Affixing a portion of a lead body to a capsule comprises at least one of peri-gland connective tissue, the outer surface of the adrenal capsule, the inner surface of the adrenal capsule, and the inner and outer surfaces of the adrenal capsule. The method of embodiment 32, comprising attaching the lead body to one.

  Example 34 The method of example 32, wherein attaching a portion of the lead body to the coating includes attaching the portion of the lead body by at least one of mechanical attachment and adhesive attachment.

  Example 35: Mechanically attaching a portion of a lead body further includes attaching the lead body to the coating using barbs, stitching tabs, a helical structure and a claw disposed with the portion of the lead body. The method of Example 34.

  While multiple embodiments are disclosed, still other embodiments of the present disclosure will become apparent to those skilled in the art from the following detailed description, which illustrates and describes exemplary embodiments of the present disclosure. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not as restrictive.

1 is an example diagram of an adrenal treatment system according to an embodiment of the present disclosure. FIG. It is a top view showing an adrenal treatment system by an embodiment of this indication. FIG. 6 is an example diagram of an adrenal therapy lead configuration according to an embodiment of the present disclosure. FIG. 6 is an illustration of another adrenal therapy lead configuration according to an embodiment of the present disclosure. FIG. 6 is an illustration of another adrenal therapy lead configuration according to an embodiment of the present disclosure. 1 is an example of an adrenal therapy lead and deployment system according to an embodiment of the present disclosure. FIG. FIG. 4D is an example view of the adrenal therapy lead shown in FIG. 4B deployed from a deployment system, according to an embodiment of the present disclosure. FIG. 4 is an exemplary view of the adrenal therapy lead shown in FIGS. 4A-4B deployed on the adrenal gland according to an embodiment of the present disclosure. FIG. 4D is an example view of the adrenal therapy lead shown in FIGS. 5 is an illustration of an adrenal therapy lead according to an embodiment of the present disclosure. FIG. 1 is an example diagram of an adrenal treatment system according to an embodiment of the present disclosure. FIG. FIG. 6 is an example diagram of another adrenal treatment system according to an embodiment of the present disclosure. FIG. 7B is an example diagram of a thermoelectric element included with the adrenal therapy system shown in FIG. 7A according to an embodiment of the present disclosure.

  While various modifications and alternative forms may be applied to the disclosure, specific embodiments are shown by way of example in the drawings and are described in detail below. However, there is no intention to limit the present disclosure to the specific embodiments described. Rather, this disclosure is intended to cover all modifications, equivalents, and alternatives falling within the scope of this disclosure as defined by the appended claims.

  In this specification, the term relating to the range of the measurement value (such as the measurement value disclosed immediately before) includes the measurement value to be described, and is close to the measurement value to be described. Adjustments and / or identifications to optimize performance and / or structural parameters with respect to calibration differences in manufacturing equipment, human error in reading and / or setting of measurements, differences in measurements related to other components Reasonably small quantities that can be easily recognized and understood by those skilled in the art as being due to inaccurate object adjustments and / or manipulations by humans or machines, and / or the like The terms “about” and “approximately” are used interchangeably to mean a measurement that includes any measurement that can differ only by It can be.

  In this specification, the term “block” may be used to imply different elements used illustratively, but this term may be any of the various blocks disclosed herein. Should not be construed as implying any particular requirement or a specific order thereof. Similarly, an exemplary method may be represented by one or more drawings (eg, a flow diagram, a communication flow, etc.), which may be any of the various steps disclosed herein. It should not be construed as meaning a requirement or any particular order thereof. However, certain embodiments may require specific steps and / or specific orders between specific steps as specified herein and / or as may be understood from their own nature. (For example, the execution of some steps may depend on the results of previous steps). Also, a “set”, “subset” or “group” of items (eg, input, algorithm, data value, etc.) can include one or more items, Subsets or subgroups of can also include one or more items. “Plurality” means more than one.

  Various aspects of the present disclosure relate to devices, methods and systems aimed at regulating neuroendocrine regulation of a patient's adrenal gland. Stimulation for chromaffin cell membranes or visceral nerves in the adrenal gland for chronic fatigue syndrome with neurotransmitter or neurohormonal dysfunction, and pain and non-pain symptoms of fibromyalgia and other medical conditions Takes effect within polarization. Adrenal chromaffin cells synthesize, store and secrete catecholamines (eg, norepinephrine, epinephrine). Stimulation of the adrenal gland increases or decreases the activity inhibition effect of multiple catecholamine biosynthetic enzymes, and increases or decreases the rate of catecholamine biosynthesis or the rate of exocytosis of chromaffin cells, or the sensitivity of chromaffin cells Can cause secretion or inhibition of catecholamines and other chromaffin granule components from chromaffin cells.

  FIG. 1 is an illustration of an adrenal treatment system 100 that includes an adrenal treatment lead 102 and a controller 104 according to an embodiment of the present disclosure. The lead 102 can include an elongated cylindrical lead body 106. The lead 102 includes a plurality of electrodes 108 disposed on the lead body 106. The electrode 108 can be disposed around the lead 102 as a ring electrode attached around the lead body 106. In an embodiment, the electrode 108 may extend at least approximately around the lead body 106. In an embodiment, one or more of the electrodes 108 may extend partially surrounding the lead body 106. In some examples, for example, the plurality of electrodes 108 can be segmented electrodes disposed axially around the lead body 106. Each of the illustrated plurality of electrodes 108 is labeled E1 to E8, but the actual number and shape of the leads and electrodes differ depending on the application.

  As shown, adrenal treatment lead 102 is operably coupled to controller 104. A connector 110 configured with the controller 104 couples the end of the adrenal therapy lead 102 to the controller 104, thereby operably (eg, communicatively, electrically and electrically) the electrode 108 to internal electronics within the controller 104. (Or physically) bind. In embodiments, the controller 104 can be configured to communicate wirelessly with one or more leads 102, in which case the controller 104 includes one or more wireless communication antennas and / or coils, etc. Can do. The controller 104 can include a housing 112 that contains and houses electronics and other components. In embodiments, the controller 104 can include a pulse generator (eg, an implantable pulse generator (IPG)) that can be implanted within the patient's body, or the controller 104 can be configured to be external to the patient. You can also In an example where the controller 104 is implantable, the housing 112 can be formed of a conductive biocompatible material such as titanium to form an airtight compartment that protects the internal electrodes from body tissues and fluids.

  The housing 112 can surround a sensing circuit 114 that is configured to receive physiological signals acquired by one or more electrodes 108 from one or more of the electrodes 108. The housing 112 can also enclose a pulse generation circuit 116 that delivers stimulation energy through one or more of the electrodes 108. According to various embodiments, the sensing circuit 114 (or aspect thereof) and / or the pulse generation circuit 116 (or aspect thereof) is configured to be implanted in the patient and / or located external to the patient. be able to. That is, for example, in embodiments, the sensing circuit 114 and the pulse generation circuit 116 can be integrated into an implantable medical device (eg, the controller 104) and / or a processor located in an external medical device. The sensing circuit 114 (or aspect thereof) and / or the pulse generation circuit 116 (or aspect thereof) can be implemented in any combination of hardware, firmware and software. For example, the sensing circuit 114 may be or include a first algorithm, a virtual processor, and / or a process implemented by the processor, and similarly, the pulse generation circuit 116 circuit may include a second algorithm, a virtual A processor, and / or a process implemented by a processor, or can include these. In an embodiment, the sensing circuit 114 may be or include a first set of physical and / or virtual circuit elements, and similarly, the pulse generation circuit 116 may be a second physical and / or It is a set of virtual circuit elements or can include them.

  In an embodiment, the controller 104 may include a programmable microcontroller or microprocessor and one or more programmable logic devices (PLDs) or application specific integrated circuits (ASICs). In some implementations, the controller 104 may include a memory. Although an embodiment of the present system 100 is shown with a controller 104 having a microprocessor-based architecture, the controller 104 (or other device) can be implemented with any logic-based integrated circuit architecture as desired. Will be understood. The controller 104 may include a digital to analog (D / A) converter, an analog to digital (A / D) converter, a timer, a counter, a filter, and / or a switch.

  The sensing circuit 114 can be configured to receive a physiological signal acquired by one or more of the electrodes 108 and analyze the received physiological signal to identify a treatment region. According to embodiments, the physiological signal may include intrinsic electrical activity and / or physiological response to the applied stimulus signal, and the like. For example, the sensing circuit 114 obtains a physiological signal that is a response to a stimulus signal administered using one or more of the electrodes 108 and analyzes the signal to identify a treatment location. It can be constituted as follows. In an embodiment, the sensing circuit 114 may be configured to evaluate patient motion, adrenal electrical activity and / or other physiological signals to identify the treatment area.

  In embodiments, the treatment area may be an area that includes a portion of the adrenal gland that has been identified as likely to be associated with an adrenal condition. Disorders such as chronic fatigue syndrome, fibromyalgia, orthostatic intolerance, irritable bowel syndrome (IBS), Crohn's disease, mood disorders / depression, or other medical conditions with neurotransmitter or neurohormonal dysfunction In the implementation used to treat, the clinician inserts the adrenal treatment lead 102 into or near one or both regions of the patient's adrenal gland associated with the disorder (eg, if the controller 104 is external). Manually, or through telemetry if the controller 104 is implanted), the controller 104 delivers stimulation energy to the selected region via one or more of the electrodes 108. Can be directed to. The controller 104 and / or clinician can determine whether the selected region is a treatment region by evaluating the electrical response acquired by one or more of the electrodes 108 (eg, If the physiological response to the stimulus shows a therapeutic effect, the selected area can be identified as the therapeutic area). In an embodiment, the clinician can identify the treatment area by identifying the adrenal area (s) whose symptoms have been at least somewhat improved by the administration of stimulation energy.

  The stimulation energy can be programmed into the controller 104, transmitted, and / or in the form of a pulsed electrical waveform to one or more of the electrodes 108 according to a similar set of stimulation parameters. For example, the stimulation parameters may include an anode (positive electrode), a combination of electrodes defining an electrode that operates as a cathode (negative electrode), on, off (zero), the proportion of stimulation energy assigned to each electrode (polarization electrode configuration), and / or Or pulse amplitude (measured in milliamps or volts, depending on whether the controller 104 supplies a constant current or a constant voltage to one or more of the electrodes 108), in microseconds Pulse duration (measured in pulse per second), pulse rate (measured in units of pulses / second), and / or burst rate (measured as stimulus on duration X and stimulus off duration Y). The electrical pulse parameters can be included. The pulse generator circuit 116 can deliver stimulation energy to one or more of the electrodes 108 via multiple channels or only one channel. Stimulation energy can be used to identify the treatment area and / or to provide stimulation treatment to the identified treatment area, or to change the treatment area over time to prevent a single point of fatigue.

  Stimulation energy can be transmitted to the tissue in a unipolar (or monopolar) or multipolar (eg, bipolar, tripolar, etc.) manner. Monopolar stimulation occurs upon activation of selected one or more of the electrodes 108 to transmit stimulation energy to the tissue. Bipolar stimulation, a type of multipolar stimulation, occurs when two of the electrodes 108 operate as an anode and a cathode, causing stimulation energy to be transmitted between the activated electrodes. Multipolar stimulation can be achieved by, for example, electrode 108 when two electrodes act as anodes and a third electrode act as a cathode, or when two electrodes act as cathodes and a third electrode acts as an anode. It can also occur when more than two of the (eg, three, four, etc.) are activated. In some examples, the pulse generator circuit 116 can individually control the magnitude of the current flowing through each electrode. In these examples, a current generator can be used to provide a current adjusted amplitude to selectively generate independent current sources for one or more of the electrodes 108.

  FIG. 2 is a plan view of an adrenal treatment system 200 according to an embodiment of the present disclosure. The adrenal therapy system 200 includes at least one implantable adrenal stimulation lead 202, 204, a pulse generator (PG) 206, an external remote controller (RC) 208, a clinician programmer (CP) 210, and an external charger 214. Can be included. In some examples, PG 206 is operatively coupled (and physically coupled in embodiments) to one or both of adrenal stimulation leads 202, 204 that can carry a plurality of electrodes 216 arranged in an array. Can do. The PG 206 can include a pulse generation circuit that delivers electrical stimulation energy in the form of a pulsed electrical waveform (ie, a temporally continuous electrical pulse) to the plurality of electrodes 216 according to a set of stimulation parameters. PG 206 may be an implantable PG (and IPG), an external PG, or may represent an operatively coupled system including one or more implantable devices and / or one or more external devices. it can.

  In some examples, RC 208 can be used to remotely control PG 206 via communication link 226. RC 208 can also modify the programmed stimulation parameters to actively control the characteristics of the electrical stimulation energy output by PG 206. The RC 208 can perform these functions by communicating indirectly with the PG 206 through the RC 208 via the communication link 228. Stimulation parameters or characteristics can be changed using CP 210. CP 210 can communicate directly with PG 206 via a communication link (not shown). The external charger 214 is a portable device used to charge the PG 206 via a charging link 230, which can be, for example, an inductive charging link, a radio frequency (RF) charging link, lighting, ultrasound and / or magnetic, etc. It can be.

  In an embodiment, the communication links 226, 228, and 230 are or may include wireless communication links, such as short-range wireless links such as, for example, Bluetooth®, IEEE 802.11, and / or dedicated wireless protocols. . In an embodiment, for example, one or more of the communication links 226, 228 and 230 may utilize Bluetooth low energy radio (Bluetooth 4.1) or a similar protocol, 2.40-2.48 GHz. An operating frequency in the range can be used. The term “communication link” can mean the ability to communicate some type of information in at least one direction between at least two devices, a direct, permanent, or otherwise restricted communication channel. It should not be understood as being limited to. That is, according to embodiments, the communication link may be a permanent communication link, an intermittent communication link, and / or an ad hoc communication link. A communication link travels directly between one or more devices via direct communication between one or more devices and / or via at least one other device (eg, repeater, router and / or hub, etc.). It can mean indirect communication. Communication links can facilitate unidirectional and / or bidirectional communication between linked devices.

  Any number of various communication methods and protocols can be used over the communication link to facilitate communication between devices in the adrenal therapy system 200. For example, wired and / or wireless communication methods can be used. For example, without limitation, wireline communication methods may include conventional copper wire communication such as DSL, broadband technology such as ISDN and cable modem, and optical fiber, and wireless communication may be cellular communication, satellite communication, radio frequency (RF) communication, infrared communication, induction, conduction and / or acoustic communication, etc. can be included.

  The exemplary components shown in FIGS. 1 and 2 are not intended to suggest limitations on the scope of use or functionality of the disclosed subject matter embodiments. In addition, these exemplary components should not be construed as having any dependency or requirement relating to any single component or combination of components illustrated herein. Further, in embodiments, any one or more of the components shown in any of FIGS. 1-2 may be replaced with various other components (and / or not shown) shown in these figures. All of which are considered to be within the scope of the disclosed subject matter. For example, in the adrenal treatment system 200, the adrenal stimulation lead described with reference to FIG. 1, FIG. 3, or FIG. 4 can be used. Further, the adrenal treatment system 200 may form part of the system described with respect to FIG.

  3A-3C are illustrations of an adrenal therapy lead 300 having a different configuration, according to an embodiment of the present disclosure. The adrenal therapy lead 300 can be used alone to perform treatment of the patient's adrenal gland or as part of an apparatus, method or system for performing treatment of the patient's adrenal gland. The adrenal treatment lead 300 can include a lead body 302 and a plurality of electrodes 304, 306, 308 disposed with the lead body 302. The adrenal therapy lead 300 is connected to a controller (eg, as shown and described with reference to FIGS. 1 and 2) and stimulates a plurality of electrodes 304, 306, 308 disposed along the lead body 302. Parameters can be supplied. The lead body 302 can be configured to attach to and engage a portion of the patient's adrenal gland. The lead body 302 can be configured to attach to a portion of the patient's adrenal gland and engage the renal fascia, gerota fascia, perirenal fat, surrounding space, prorenal paraspace, capsule or cortex. . Also, as described in detail with reference to FIGS. 5-6, for example, at least one of the plurality of electrodes 304, 306, 308 regulates catecholamine release from chromaffin cells in the adrenal gland. Configured to deliver stimulation energy. The adrenal therapy lead 300 can also include a button 310 configured to facilitate attachment and stimulation of the lead to the adrenal gland and a helical anchor 312. Also, one or more of the plurality of electrodes 304, 306, 308 can be configured to sense catecholamines released as a result of delivered stimulation energy. The button 310 can be formed of a material having the same characteristics as the lead body 302. In some examples, the button 310 can be sized and shaped to provide a greater stimulation surface area relative to the lead body 302 by disposing a plurality of electrodes 304, 306, 308 on the button 310.

  The button 310 can have greater flexibility than the lead body 302 and can be configured to fit the adrenal gland to which it is attached. Specifically, the button 310 can assume the shape of the adrenal gland when attached to the adrenal gland. Further, the button 310 may have a width that is narrower than the width of the lead body 302. In some examples, the button 310 can be part of an adrenal therapy lead 300 that attaches to a part of the adrenal gland. The adrenal gland is surrounded by a fat capsule. The button 310 can be attached to the outer surface of the capsule, within the capsule, to the inner surface of the capsule (eg, between the capsule and the adrenal gland), or directly to the adrenal gland. Accordingly, the width of the button 310 can be approximately equal to or narrower than the adrenal capsule.

  The helical anchor 312 can be configured to fix the lead body 302 directly or indirectly (via the capsule) to the adrenal gland. In some examples, in addition to electrodes 304, 306, 308, helical anchor 312 can also be configured as an electrode. The length of the helical anchor 312 can depend on the anchoring position (eg, longer when anchored to the adrenal gland than when anchored to the capsule or adrenal parenchyma). The helical anchor 312 can be configured to relieve movement of the lead body 302 upon implantation to ensure positive fixation on the adrenal gland.

  Also, the button 310 can be disposed along any part of the lead body 302. As shown in FIG. 3A, the button 310 is disposed along an intermediate portion of the lead body 302. The lead body 302 includes some of the plurality of electrodes 304, 306, 308 on one side of the button 310 and the remainder of the plurality of electrodes 304, 306, 308 on the other side of the button 310. In some examples, the position of the button 310 may be adjusted after the button 310 is implanted and / or fixed relative to the adrenal gland. The button 310 can frictionally engage the lead body 302 such that the physician's applied force overcomes the coupling of the button 310 to the lead body 302. The button 310 can also be attached or bonded to the lead body 302 with a medical adhesive. The physician can adjust the position of the button 310 before the lead body 302 is implanted or after the button 310 is secured to the adrenal gland. As a result, the physician positions the plurality of electrodes 304, 306, 308 relative to the adrenal gland by displacing the button 310 along the length of the lead body 302 before or after implantation and / or fixation of the button 310 relative to the adrenal gland. Can be adjusted. As shown in FIG. 3B, the button 310 can also be coupled or attached to the distal end of the lead body 302. In some examples, the distal end of the lead body 302 can include a plurality of buttons 310.

  As shown in FIG. 3C, a plurality of electrodes 304, 306, and 308 can be arranged around the outer periphery of the button 310. In some examples, this arrangement of multiple electrodes 304, 306, 308 can facilitate the induction of stimulation energy to a narrow target site rather than the entire length of the lead body 302.

  FIG. 4A is an illustration of an adrenal therapy lead 400 and deployment system 402 according to an embodiment of the present disclosure. As shown in FIG. 4A, the adrenal treatment lead 400 is disposed within the deployment system 402. The adrenal therapy lead 400 can be used alone to perform treatment of the patient's adrenal gland or as part of an apparatus, method or system for performing treatment of the patient's adrenal gland. The adrenal treatment lead 400 can include a paddle element 404. The deployment system 402 can have a cylindrical shape that includes a circular opening at the distal end. The delivery system 402 can be loaded with an adrenal therapy lead 400 including a lead body 406 at either end. When loading the adrenal therapy lead 400, the paddle element 404 can collapse within the deployment system 402. As shown in FIG. 4A, the paddle element 404 can be rolled up and collapsed within the deployment system 402. In some examples, the paddle element 404 can be folded, creased, creased, or bent and collapsed within the deployment system 402. In some examples, deployment system 402 can be a delivery catheter.

  FIG. 4B is an example view of the adrenal therapy lead 400 shown in FIG. 4B deployed from the deployment system 402, according to an embodiment of the present disclosure. FIG. 4B shows the adrenal treatment lead 400 in the deployed / delivery configuration, and FIG. 4A shows the adrenal treatment lead 400 in the delivery configuration. The paddle element 404 is configured to expand to the deployed configuration shown in FIG. 4B in response to deployment from the deployment system 402 and bend and collapse to the delivery configuration shown in FIG. 4A in response to retraction within the deployment system 402. can do.

  Also, as shown in FIG. 4, the paddle element 404 can include a plurality of electrodes 408. A plurality of electrodes 408 are disposed on a paddle element 404 that can be disposed at the distal end of the lead body 406. The plurality of electrodes 408 can be configured to deliver stimulation energy that regulates the release of catecholamines from chromaffin cells in the patient's adrenal glands. Adrenal therapy lead 400 may be connected to a controller (eg, as shown and described with reference to FIGS. 1 and 2) to provide stimulation parameters to a plurality of electrodes 408 disposed with paddle element 404. it can. One or more of the plurality of electrodes 408 can also be configured to sense biomarkers that are affected by the delivered stimulation energy. By providing the sensed level of released catecholamine as feedback to the controller, the stimulation energy can be varied to achieve the desired level of catecholamine release. In some examples, the paddle element 404 can include a thermoelectric element 410 disposed together. The thermoelectric element 410 can provide a cooling effect on the adrenal gland. As described in detail with reference to FIGS. 7A-7B, the thermoelectric element 410 that cools the adrenal gland can also regulate the release of catecholamines from chromaffin cells in the adrenal gland. Specifically, the thermoelectric element 410 (eg, a Peltier element) can be configured to cool the adrenal gland area. Application of the thermoelectric element 410 to the medulla (in, on or near) can have the effect of regulating the circulating level of catecholamines in the bloodstream. In some examples, the thermoelectric element 410 can provide a cooling effect within the arterial supply to the adrenal gland, within or near the vascular lumen. The thermoelectric element 410 can provide cooling in the temperature range of 4 degrees Celsius to 32 degrees Celsius.

  In some examples, lead body 406 or a portion thereof can be configured to attach to a portion of a patient's adrenal gland. Specifically, the paddle element 404 or lead body 406 can be configured to engage one adrenal capsule. As described above, the paddle element 404 is flexible and can be configured to engage and adhere to a portion (eg, a capsule) of a patient's adrenal gland in a delivery configuration. The paddle element 404 can be at least partially adapted to the adrenal gland to mitigate the resistance of the adrenal treatment lead 400. In some examples, the resistance of the adrenal therapy lead 400 can be further mitigated by embedding a paddle element 404 between the capsule and the adrenal gland. In other examples, the lead body 404 and / or the paddle element 404 may include a (single) barb, a (single) rigid helical structure and / or a (nail) claw for mechanical attachment to the adrenal gland. (Talon) (not shown). The lead body 406 can also include a suture feature (eg, a suture hole through which a suture can pass) to secure the lead body 406 in place. In other examples, in addition to or instead of the mechanical attachment mechanism, tissue glue on the lead body 406 and / or paddle element 404 to adhesively attach the lead body 406 and / or paddle element 404 to the adrenal gland, Adhesives and / or hydrogels or hydrogel / polymer types can be applied.

  FIG. 4C is an illustration of the adrenal therapy lead 400 shown in FIGS. 4A-4B deployed on the adrenal gland 412 according to an embodiment of the present disclosure. As shown in FIG. 4C, the paddle element 404 is configured to bend and engage and attach to a portion of the adrenal gland 412. A physician placing the adrenal therapy lead 400 can visualize the orientation of the plurality of electrodes 408 by fluoroscopy. In other examples, one or both of the lead body 406 and the paddle element 404 can include radiopaque markers (not shown) that assist in the visualization of the adrenal treatment lead 400. In some examples, the paddle element 404 can be a wrap or mesh.

  4D is an illustration of the adrenal therapy lead 400 shown in FIGS. 4A-4C including tethers 414, 416, according to an embodiment of the present disclosure. Tethers 414, 416 can be attached to paddle element 404 to assist in repositioning paddle element 404 relative to adrenal gland 412. Tethers 414, 416 can extend along the lead body 406 from the paddle element 404. In some examples, the tethers 414, 416 can extend along the entire length of the lead body 406 so that a physician or user can manipulate the tethers 414, 416. In other examples, the tethers 414, 416 can be attached to a portion of the lead body 406 such that manipulation of the lead body 406 indirectly manipulates the tethers 414, 416 and the paddle element 404. When tension is applied to the tethers 414, 416, the paddle element 404 can be pulled back into the deployment system 402. As a result, tension can be applied to the tethers 414, 416 after deployment from the deployment system 402 or after complete removal of the adrenal treatment lead 400 to allow repositioning of the paddle element 404. Specifically, the paddle element 404 can be reconfigured to a delivery configuration as shown in FIG. 4A and redeployed if the placement of the paddle element 404 is desired, or removed from the adrenal gland 412 with the deployment system 402. .

  FIG. 5 is an illustration of an adrenal therapy lead 500, 502 according to an embodiment of the present disclosure. The illustrated adrenal therapy leads 500, 502 are disposed on the patient's adrenal glands 504, 506. Adrenal glands 504, 506 are located above the patient's kidneys 508, 510 located on either side of the patient's vena cava 512 and aorta 514. The adrenal therapy leads 500, 502 can be delivered and attached directly or indirectly to the adrenal glands 504, 506 (or gelota fascia) by laparoscopic surgery, open surgery or other minimally invasive surgery.

  Each of the adrenal therapy leads 500, 502 can have a lead body 516, 518 and a plurality of electrode sets 520, 522 disposed with the lead body 516, 518. The plurality of electrode sets 520, 522 can be disposed longitudinally along the adrenal glands 504, 506. In some examples, the distal portion of each lead body 516, 518 (eg, the portion having a plurality of electrode sets 520, 522) is more flexible (eg, flexible) than the other portions of the lead bodies 516, 518. Or the distal portion of each lead body 516, 518 can be formed of other materials (Pebax®, polyethylene, or Hytrel® (polyester)). Flexibility added to the lead body 516, 518 or a portion of the lead body 516, 518 may assist in mitigating movement of the adrenal treatment leads 500, 502 when attached to the adrenal glands 504, 506. The flexibility added to a portion of the lead body 516, 518 acts as a strain relief mechanism so that movement of other portions transmitted to other portions of the lead body 516, 518 is isolated and / or indirectly absorbed. Can function. In other examples, additional lengths or slacks between the adrenal glands 504, 506 and the implantation position of the controller coupled to each lead body 516, 518 are used to provide each lead body 516, 518 of the adrenal treatment leads 500, 502. Can be attached to the adrenal glands 504, 506 to provide additional flexibility to absorb patient movement.

  Each lead body 516, 518 can also include buttons 524, 526. The buttons 524, 526 of each lead body 516, 518 can have greater flexibility than each lead body 516, 518 and can be configured to fit and attach to the adrenal glands 504, 506. Specifically, each button 524, 526 can take the shape of an adrenal gland 504, 506. The adrenals 504, 506 are surrounded by a fat capsule (as shown in more detail in FIG. 6). Each button 524, 526 can be attached to the outer surface of the capsule, within the capsule, to the inner surface of the capsule (eg, between the capsule and the adrenal gland), or directly to the adrenal glands 504, 506.

  In some examples, each lead body 516, 518 and / or each button 524, 526 is barbed (s) for mechanical attachment (not shown) to the adrenal glands 504, 506, hard (s) It may include a helical structure and / or claw (s). In other examples, each lead body 516, 518 and / or each button 524, 526 is attached to each lead body 516, 518 and / or each button 524, 526 for attachment to the adrenal glands 504, 506 in addition to or instead of the mechanical attachment mechanism. A hydrogel can be applied.

  As described above, the adrenal therapy leads 500, 502 can be connected to a controller (eg, as illustrated and described with reference to FIGS. 1 and 2). The controller delivers stimulation energy that regulates the release of catecholamines from chromaffin cells in at least one of the adrenal glands 504, 506 through one or more of the electrodes in the plurality of electrode sets 520, 522. Can be configured to command. In some examples, the controller is configured to command intermittently or continuously to deliver stimulation energy through one or more different combinations of the electrodes in the plurality of electrode sets 520, 522. Can do. In particular, a controller (not shown) can stimulate energy at a duty cycle based on catecholamine metabolism time or patient clinical signs through one or more of the electrodes in the plurality of electrode sets 520, 522. May be included (eg, as described with reference to FIG. 1). This duty cycle applies the stimulus over 25% of a period (eg, minutes, 1 hour or 1 day) and holds the stimulus over 75% of this period (eg, minutes, 1 hour or 1 day) Can be included. Continuous stimulation through one or both of the adrenals 504, 506 need not necessarily reach a therapeutic level of catecholamines. Stimulation energy delivery duty cycle control can reduce battery consumption and reduce the likelihood of a decaying effect over time due to adaptation or exhaustion of the adrenal glands 504,506. The stimulation energy is a frequency of 2 Hz to 20 kHz (for example, 2 Hz to 50 Hz, 50 Hz to 100 Hz, 100 Hz to 500 Hz, 500 Hz to 1 kHz, 1 kHz to 5 kHz, 5 kHz to 10 kHz, 10 kHz to 20 kHz, or any combination thereof). Can be sent out. Stimulation energy can be applied when the burst of energy includes pulses with a frequency between 2 Hz and 20 kHz, or continuously. Also, the frequency and / or pulse width stimulation energy can be varied continuously or periodically with time. Varying the current, frequency and / or pulse width can reduce the potential for attenuating effects of stimulation over time due to adaptation of the adrenal glands 504,506. In these examples, any delivered stimulation energy can be changed in response to patient feedback based on the patient's physical symptoms.

  Also, the stimulation energy can be transmitted to the adrenal glands 504, 506 in a monopolar or multipolar (eg, bipolar, tripolar, etc.) manner. Monopolar stimulation occurs upon activation of selected one or more of the electrodes of the plurality of electrode sets 520, 522 to transmit stimulation energy to the tissue. Bipolar stimulation, which is a type of multipolar stimulation, occurs when two of the electrodes in the plurality of electrode sets 520 and 522 operate as an anode and a cathode, and stimulation energy is transmitted between the activated electrodes. . Multipolar stimulation can occur in multiple ways, for example when two electrodes act as anodes and a third electrode acts as a cathode, or when two electrodes act as cathodes and a third electrode acts as an anode. It can also occur when more than two (eg, three, four, etc.) of the electrodes in electrode set 520, 522 are activated. The stimulation energy can also be split across one or more of the electrodes in the plurality of electrodes 520 and individually across one or more of the electrodes in the plurality of electrodes 522.

  In some examples, the controller can command delivery of stimulation energy to one of the adrenals 504, 506 at some point. The controller also tests the electrode sets 520, 522 to determine which of the electrode sets 520, 522 achieves the desired response (eg, based on measuring patient feedback and / or patient catecholamine levels). It can also be determined. Specifically, in some examples, one of the adrenal glands 504, 506 may respond to the stimulus differently than the other of the adrenal glands 504, 506. Thus, the controller changes the delivery of stimuli to one or both of the adrenal glands 504, 506 to achieve a desired response in response to physiological sensor measurements and / or patient input. Can be made. Stimulation energy can be delivered to one or both of the electrode sets 520, 522 to adjust the stimulation of the adrenal glands 504, 506. Both adrenal glands 504, 506 can be stimulated simultaneously, or the stimuli applied to the adrenal glands can be alternated (eg, according to a duty cycle as described above). In some examples, co-stimulation of the adrenal glands 504, 506 can reduce the likelihood of a decaying effect over time due to adaptation / tolerance of the adrenal glands 504, 506. By providing the sensed level of released catecholamine as feedback to the controller, the stimulation energy can be varied to achieve the desired level of catecholamine release.

  The exemplary components shown in FIG. 5 are not intended to suggest limitations on the scope of use or functionality of embodiments of the disclosed subject matter. In addition, these exemplary components should not be construed as having any dependency or requirement relating to any single component or combination of components illustrated herein. Further, in embodiments, any one or more of the components shown in any of FIGS. 1-4 may be replaced with various other components (and / or not shown) shown in these figures. All of which are considered to be within the scope of the disclosed subject matter. For example, the adrenal stimulation leads 500, 502 may be used in connection with the system described with reference to FIGS. Adrenal stimulation leads 500, 502 may also include a helical anchor 312 as shown in FIG. 3, or a thermoelectric element 410 or paddle element 404 as shown in FIG.

  FIG. 6 is an illustration of an adrenal treatment system 600 according to an embodiment of the present disclosure. Adrenal therapy system 600 includes a controller 602 (eg, a pulse generator) that houses electronic components and other components, an adrenal stimulation lead 604 coupled to controller 602, and optionally a physiological sensor 606. The adrenal stimulation lead 604 can include a lead body 608 configured to engage the adrenal gland 610 of the patient 620. Specifically, the lead body 608 can be configured to engage the capsule 612 of the adrenal gland 610. FIG. 6 also includes an insertion portion highlighting the anatomy of the adrenal gland 610. The capsule 612 surrounds the adrenal gland 610 located above the kidney 622. The lead body 608 can be attached to the outer surface of the coating 612, within the coating 612, and to the inner surface of the coating 612 (eg, between the coating of the adrenal gland 610 and the rest). The adrenal gland 610 further includes a cortex 614 and a medulla 616 that produce steroid hormones. Chromaffin cells in medulla 616 synthesize, store and secrete catecholamines (eg, norepinephrine, dopamine). The lead body 608 can also attach to the cortex 614 or medulla 616 (eg, through the mechanical attachment mechanism described with reference to FIGS. 3A-3C, or the adhesive attachment mechanism).

  The lead body 608 also includes a plurality of electrodes 618 disposed along the lead body 608. The plurality of electrodes 618 can be configured to deliver stimulation energy that modulates the release of catecholamines from chromaffin cells in the adrenal gland 610 through at least one of the plurality of electrodes 618. A controller 602 that is physically connected to the lead body 608 and electrically coupled to the plurality of electrodes 618 is capable of catecholamine release from the chromaffin cells through one or more of the plurality of electrodes 618. It can be configured to instruct to deliver a stimulating energy to regulate. Stimulation energy can be transmitted to the adrenal gland 610 in a monopolar or multipolar (eg, bipolar, tripolar, etc.) manner. Monopolar stimulation occurs upon actuation of one or more selected electrodes of the plurality of electrodes 618 to transmit stimulation energy to the tissue. Bipolar stimulation, which is a type of multipolar stimulation, occurs when two of the electrodes 618 operate as an anode and a cathode, and stimulation energy is transmitted between the activated electrodes. Multipolar stimulation can occur in multiple ways, for example when two electrodes act as anodes and a third electrode acts as a cathode, or when two electrodes act as cathodes and a third electrode acts as an anode. It can also occur when more than two (eg, three, four, etc.) of the electrodes in electrode set 618 are activated. Stimulation energy can also be split across one or more of the electrodes in the plurality of electrodes 618. The level of released catecholamine can be sensed by the physiological sensor 606 and provided as feedback to the controller 602 to change the stimulation energy to achieve the desired catecholamine release level.

  In some examples, the controller can be configured to command intermittent or continuous delivery of stimulation energy through one or more different combinations of the plurality of electrodes 618. The controller 602 also commands delivery of stimulation energy at a duty cycle based on catecholamine metabolism time through one or more of the plurality of electrodes 618 (eg, as described with reference to FIG. 1). It is also possible to include a circuit. This duty cycle applies the stimulus over 25% of a period (eg, minutes, hours or days) and holds the stimulus over 75% of this period (eg, minutes, hours or days) Can be included. Duty cycle control of stimulus energy delivery can reduce battery consumption of the controller 602. Further, the stimulation energy can be transmitted at a frequency of 2 Hz to 20 kHz. Stimulation energy can be applied when the burst of energy includes pulses with a frequency between 2 Hz and 20 kHz, or continuously. It is also possible to vary the frequency and / or pulse width stimulation and / or current energy continuously or periodically with time.

  The delivered stimulation energy can be changed in response to patient 620 feedback based on patient 620 physical symptoms. The controller 602 can also command a change in stimulation energy delivered to one or more of the plurality of electrodes 618 based on patient feedback. Treatment is based on changes in physical symptoms or data acquired by physiological sensor 606 and / or based on patient 620 or physician input on an external device communicatively coupled to controller 602 that can control stimulation energy levels. It can be customized by calibrating to the target release level of catecholamines. Patient 620 can enable / disable treatments that correlate with their own perception of their symptoms (eg, treatment can be enabled when they feel symptoms of chronic fatigue). In these scenarios, the controller 602 includes a self-limiting mechanism to avoid catecholamine depletion so that the patient does not cause catecholamine depletion by requiring continued treatment (eg, after a period of time, the controller 602 is stimulated). Can be down-regulated or turned off).

  In some examples, physiological sensor 606 can be configured to measure at least one physiological response of patient 620. In addition to being communicatively (and physically) coupled to lead 604, controller 602 can be communicatively coupled to physiological sensor 606. The controller 602 can be configured to receive a signal from the physiological sensor 606 having data indicative of at least one physiological response of the patient 620. The communication between the controller 602 and the physiological sensor 606 may be a wireless communication such as a short-range wireless link such as Bluetooth, IEEE 802.11 and / or a dedicated wireless protocol (as described in detail with reference to FIG. 2), for example. Links, or may include these wireless communication links. Controller 602 can analyze the signal from physiological sensor 606 to calculate a change in stimulation energy and communicate with lead 604 to change the stimulation energy based on the analysis of the signal.

  In some examples, the physiological sensor 606 can be an independent sensor configured to receive a physiological signal. In other examples, the physiological sensor 606 can be the controller 602 itself. Further, the physiological sensor 606 may be a remotely embedded monitoring system or wearable monitoring system (in communication with the controller 602). The physiological sensor 606 may also be an independent sensing lead that connects to the controller 602. This independent sensing lead can monitor a signal from another target remote from the adrenal gland 610 of the patient 620 (eg, indicating blood pressure) and capture one or more physiological signals. The adrenal therapy system 600 can include one or more of these aspects as a physiological sensor 606.

  In some examples, the physiological sensor 606 may include a heart rate of the patient 620, a heart rate variability of the patient 620 (such as adjusting S1 / S2 amplitude with respiration), a respiratory rate of the patient 620, an activity level of the patient 620, a patient 620, Catecholamine levels (eg, chemical sensors), patient 620 metanephrine levels, metanephrine: creatinine (urine) ratio level, metanephrine as a surrogate for plasma norepinephrine, position, patient 620 body temperature, adrenal 610 temperature, patient 620 heart It may be configured to measure at least one of stroke volume and patient 620 arterial pressure, or any combination thereof (eg, heart rate / respiration rate ratio). The activity level of the patient 620 helps inform the controller 602 whether the stimulation energy should be changed (eg, increased or blocked) due to the magnitude of the change shown in the circulation and the magnitude of the catecholamine in the circulation. be able to. In some examples, a physiological sensor 606 can be implanted in the bladder to measure urinary metanephrine levels in a patient 620 that is a surrogate for norepinephrine levels. Changes in the physiological response described above may require regulation of catecholamine exocytosis or metabolism so that the required change in physiological response is obtained. As a result, the controller 602 can change (increase or decrease) the stimulation energy that regulates the release of catecholamines from the adrenal gland 610 to maintain a desired catecholamine level in the patient 620.

  In some examples, the physiological sensor 606 can be configured to measure the temperature of the patient 620. Physiological sensor 606 indicates (via an intra-arterial or peri-arterial approach) cardiac output of patient 620, cardiac stroke volume (e.g., S1 indicating contractility or blood pressure changes due to exchange nerve activity). S2), may also be configured to measure heart contractility and / or mean arterial pressure / pulse pressure / cardiac contraction / diastole. Physiological sensor 606 is a surrogate for other catecholamine levels or various medical conditions involving neurohormonal or neurotransmitter dysfunction, such as fibromyalgia (eg, as indicated by fatigue), chronic fatigue or sleep apnea. Pain symptoms or non-pain symptoms can also be measured. In some examples, the physiological sensor 606 may be a proxy for catecholamine levels associated with postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), orthostatic intolerance (OI), or heart failure and It can be configured to measure surrogate catecholamine levels associated with migraine, all of which have causes and consequences due to changes in circulating catecholamine levels. The physiological sensor 606 may also measure a decrease in positive expiratory pressure (PEP), a decrease in untreated left ventricular ejection time (LVET), and / or an increase in LVET corrected for heart rate. Changes in the physiological responses described above may require regulation of catecholamine metabolism and exocytosis. As a result, the controller 602 can adjust the stimulation energy that regulates the release of catecholamines from the adrenal gland 610 to maintain the desired catecholamine levels in the patient 620.

  Co-stimulation provided by the controller 602 can result in a closed loop system that uses systemic catecholamines or disease state markers to optimize treatment. In some examples, two or more physiological parameters provide the controller 602 with closed loop control, allowing predictive power to deliver therapy only when needed, or therapy titration (eg, stimulus amplitude ) To optimize clinical outcomes by allowing different improvements in charge). The system 600 uses multiple physiological sensors 606 in communication with the controller 602 as described above to address steady or temporary deficiency (the ability to quickly rise / fall) of the adrenal gland (s) 610. can do. The sensor can perform further quantification, measurement, and tracking of catecholamine levels or pathology as a function of activity to optimize treatment. The controller 602 can collect and aggregate measurements of various physiological sensors to change the delivery of stimulation energy delivered through the plurality of electrodes 618.

  Physiological sensor 606 can measure a steady deficiency in the catecholamine level of patient 620 by identifying a physiological response at a given steady state activity level measured by physiological sensor 606. Temporary deficiency can be monitored by examining “temporary” physiological sensor 606 measurements around the transition of activity. In some instances, with respect to maintaining patient 620 catecholamine levels, the desired response is quick, rather close to a “underdamped” system, whereas inferior performance appears to be an overdamped system. In some examples, the controller 602 can be programmed based on patient customization. For example, some patients may prefer stimulating energy with low systemic catecholamines. Accordingly, the controller 602 can be programmed to repeat the stimulus in this manner. Another patient may prefer a high systemic catecholamine status that results in different stimulating energy (eg, compared to a patient that prefers low systemic catecholamine). The controller 602 can be programmed with criteria in the patient so that the stimulation energy can change based on activity level and time of day (wake / sleep). Biomarker data can also be used to calibrate patient preferences (increase or decrease) in systemic catecholamine levels in a closed loop system for each patient.

  As a specific example, physiological sensor 606 can be configured to monitor heart rate activity. The physiological sensor 606 continuously records heart rate (HR) and activity (motion) information, or body position (eg, orthostatic imbalance) (eg, using an accelerometer) in the patient 620, and a data stream. Can be analyzed into discrete activity bands. The time axis is separated from the viewpoint of transition between activity bands. HR data around the transition provides an indication of temporary deficiency, while HR data from between transitions and well away from the transition can yield steady deficiency data. In some examples, the physiological sensor 606 can measure heart sounds instead of or in conjunction with monitoring the heart rate of the patient 620. Heart sounds can provide an indication of whether patient 620 is waking up or sleeping, affecting the regulation of catecholamine levels. Specifically, when the patient 620 is sleeping, the controller 602 optimizes (decreases) the catecholamine level by reducing the stimulation level delivered through the plurality of electrodes 618 compared to when the patient is awake. ) Can be programmed to avoid insomnia. Maintain stimulation parameters to ensure that catecholamine levels are above the lower limit (low circulating catecholamine levels can be related to the patient currently having insomnia challenges) or stay below the upper limit It can also be made. Also, during the exercise of the patient 620, the controller 602 ensures an optimal level to reduce pain and fatigue (eg, adjusting the level based on a baseline change to struggle or stress) and catecholamine levels. It can be ensured that it stays above the lower limit (high circulation levels can be related to the current problem that these patients are less resistant to prolonged activity). As a result, the controller 602 can be configured to ensure proper adjustment of catecholamine levels that can change during patient exercise, rest, or stress experiences.

  The exemplary components shown in FIG. 6 are not intended to suggest limitations on the scope of use or functionality of embodiments of the disclosed subject matter. In addition, these exemplary components should not be construed as having any dependency or requirement relating to any single component or combination of components illustrated herein. Further, in embodiments, any one or more of the components shown in any of FIGS. 1-5 may be replaced with various other components shown in these figures (and / or not shown). All of which are considered to be within the scope of the disclosed subject matter. For example, the adrenal stimulation lead 602 may be used in connection with the system described with reference to FIGS. The adrenal stimulation lead 604 may also include a helical anchor 312 as shown in FIG. 3 or a thermoelectric element 410 or paddle element 404 as shown in FIG.

  FIG. 7A is an illustration of another adrenal treatment system according to an embodiment of the present disclosure. FIG. 7 illustrates various aspects of a patient's anatomy 700 including an aorta 702, a vena cava 704, a right kidney 706, a left kidney 708, a right adrenal gland 710, and a left adrenal gland 712. A pulse including an upper right adrenal artery 714, a right middle adrenal artery 716, a right lower adrenal artery 718, a left upper adrenal artery 720, a left middle adrenal artery 722, a left lower adrenal artery 724, and right and left lower phrenic arteries 726 Some aspects of the tube structure are highlighted. The adrenal therapy system can include attaching or coupling thermoelectric elements (shown in FIG. 7B) to one or more locations 728a-h of the vasculature. The thermoelectric element can cool one or both of the adrenal glands 710, 712 to regulate the release of catecholamines from chromaffin cells.

  7B is an illustration of a cooling system 730 included with the adrenal therapy system shown in FIG. 7A, according to an embodiment of the present disclosure. The cooling system 730 can be attached to one or more locations 728a-h shown in FIG. 7A. The cooling system 730 cools the blood flow to the adrenal glands 710, 712 at locations 728a-h. Cooling the blood can cool the perinephric region of the adrenal gland 710, 712 that can cause the release of catecholamines from chromaffin cells in the adrenal glands 710, 712. As a result, the cooling system 730 can increase the levels of norepinephrine and dopamine circulating in the bloodstream, similar to stimulation of the adrenal glands 710, 712. The cooling system 730 can be used alone or in combination with the stimulation system and leads described herein (eg, FIGS. 1-6). Specifically, the cooling system 730 can include a controller 732. Controller 732 can apply a current to provide a cooling effect. The controller 732 can also be coupled to an adrenal stimulation lead as described herein (eg, FIGS. 1-6) to control the stimulation provided to the adrenal glands 710, 712. The controller 732 can provide cooling and stimulation simultaneously or alternately. As a result, it is possible to extend the battery life of the controller 732 by suppressing battery consumption, and to reduce the possibility of a decaying effect over time due to the adaptation or consumption of the adrenals 710 and 712.

  The cooling system 730 can include at least one thermoelectric element (eg, a Peltier element) to enhance the cooling effect of the adrenal glands 710, 712. As shown in FIG. 7B, a stent or wrap 744 is placed at one of the vasculature locations 728a-h in or around the artery 742. In some examples, a stent or wrap 744 can be placed directly on one or both of the adrenals 710, 712. Stent or wrap 744 includes a thermoelectric element coupled to controller 730 via insulated wires 738, 740. The controller 732 can apply currents 734 and 736 through the insulated wires 738 and 740 to dissipate heat generated from the thermoelectric elements. The cooling system 730 can provide cooling in the temperature range of 4 degrees Celsius to 32 degrees Celsius.

  The exemplary components shown in FIGS. 7A-7B are not intended to suggest limitations on the scope of use or functionality of embodiments of the disclosed subject matter. In addition, these exemplary components should not be construed as having any dependency or requirement relating to any single component or combination of components illustrated herein. Further, in embodiments, any one or more of the components shown in any of FIGS. 7A-7B may be replaced with various other components (and / or not shown) shown in these figures. All of which are considered to be within the scope of the disclosed subject matter. For example, the cooling system 730 may be used in connection with the system described with reference to FIGS. 1 and 2 or the adrenal stimulation lead and system described with reference to FIGS.

  Various modifications and additions may be made to the described exemplary embodiments without departing from the scope of the present disclosure. For example, although specific features have been referred to in the above-described embodiments, the scope of the present disclosure also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Accordingly, the scope of the present disclosure is intended to embrace all such alternatives, modifications and variations that fall within the scope of the claims, and all equivalents thereof.

Claims (15)

A device for treating a patient's adrenal gland,
A lead body configured to attach to a portion of the patient's adrenal gland and engage the adrenal capsule;
A plurality of electrodes disposed along the lead body;
Wherein at least one of the plurality of electrodes is configured to deliver stimulation energy that regulates the release of catecholamines from chromaffin cells in the adrenal gland.
A device characterized by that. The lead body is configured to adhere to the capsule or surrounding connective tissue of the adrenal gland;
The apparatus of claim 1. The lead body is at least one of connective tissue around the capsule, the outer surface of the capsule of the adrenal gland, the inner surface of the capsule of the adrenal gland, and the inner surface and the outer surface of the capsule of the adrenal gland. Configured to adhere,
The apparatus according to claim 1 or 2. The lead body attaches to the part of the adrenal gland of the patient by at least one of mechanical attachment and adhesive attachment of the lead body to the part of the adrenal gland of the patient or connective tissue around the capsule. Composed of,
The apparatus according to claim 1. The lead body further includes at least one of a barb, a suture tab, a helical structure and a claw for mechanical attachment of the lead body to the portion of the adrenal gland of the patient;
The apparatus according to claim 4. Further comprising at least one of tissue glue, adhesive and hydrogel for attachment of the lead body to the portion of the adrenal gland of the patient;
The apparatus according to claim 4. At least one of the plurality of electrodes includes a perforated portion and is configured to enter the adrenal gland;
The apparatus according to claim 1. The at least one of the plurality of electrodes configured to enter the adrenal is further configured to deliver the stimulation energy that regulates the release of catecholamines from chromaffin cells in the adrenal. To be
The apparatus according to claim 7. The patient's heart rate, the patient's heart rate variability, the patient's respiratory rate, the patient's activity level, the patient's catecholamine level, the patient's catecholamine metabolism, the patient's normetanephrine level, the patient's metanephrine level The patient's urinary creatinine level, the patient's cortisol metanephrine level, the patient's posture, the patient's body temperature, the patient's cardiac output, the patient's arterial pressure, the patient's sleep state, and the patient A physiological sensor configured to measure at least one of the sleep depths of
The device according to claim 1. The stimulation energy is changed in response to at least one of the measurement of the physiological sensor and an input from the patient;
The apparatus according to claim 9. A controller configured to communicate with the physiological sensor and to command delivery of the stimulation energy in response to the communication;
The apparatus according to claim 9. A controller configured to command the stimulation energy to regulate the release of catecholamines from chromaffin cells in the adrenal gland through at least one of the plurality of electrodes;
The apparatus according to claim 1. The controller is configured to command intermittently or continuously to deliver the stimulation energy through different electrode sets of the plurality of electrodes.
The apparatus according to claim 12. The controller is configured to instruct to deliver the stimulation energy through a duty cycle based on catecholamine metabolism time through at least one of the plurality of electrodes.
The apparatus according to claim 12. The controller is configured to instruct delivery of the stimulation energy at a frequency between 2 Hz and 20 kHz through at least one of the plurality of electrodes;
The apparatus according to claim 12.

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